Epidermal growth factor receptor and insulin-like growth factor-I receptor expression and function in human soft-tissue sarcoma cells.
Epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) receptors are implicated in the development and progression of several malignancies including osteogenic and soft tissue sarcomas (STS). To determine a role for ligand-mediated receptor activation in sarcoma progression, the relative expression and function of EGF-R, IGF-I-R, and several other molecular determinants implicated in the progression of mesenchymal neoplasms were evaluated in human sarcoma cells established from surgical specimens of primary and metastatic tumors. mRNA blot analyses demonstrated the expression of c-Met, p53, and MDM2-specific transcripts. Western blot analyses confirmed the production of high levels of p53 protein; however, minimal levels of MDM2 and c-Met proteins were detected. Analysis of STS cells #23, #26, and #50 originating from an unclassified sarcoma lung metastasis, a malignant fibrous histiocytoma lung metastasis, and a dedifferentiated chondrosarcoma, respectively demonstrated high steady-state levels of EGF-R and IGF-I-R mRNA transcripts and protein correlating with receptor-specific tyrosine kinase activity and autophosphorylation in response to ligand. Treatment of these STS cells with EGF resulted in a >5 fold increase in DNA synthesis and mitogenesis compared with untreated controls. In contrast, treatment with IGF-I showed a variable STS growth response correlating with the origin of the tumor. These data support the involvement of EGF-R and IGF-I-R in the growth and metastasis of human soft tissue sarcoma and may offer new targets for therapeutic intervention in the management of this disease.
Beech
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Departments of Cell Biology and Surgical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA.
Pollock
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RE
Tsan
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R
Radinsky
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R
D015153:Blotting, Western; D004273:DNA, Neoplasm / Q000096:biosynthesis; D066246:ErbB Receptors / Q000378:metabolism* / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000502:physiology; D009362:Neoplasm Metastasis / Q000473:pathology; D009687:Nuclear Proteins; D010012:Osteogenesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases